Association between Common CYP1 A2 Polymorphisms and Theophylline Metabolism in Non-smoking Healthy Volunteers.

This study was designed to investigate the impact of cytochrome P450 ( CYP) 1 A2 polymorphisms on theophylline metabolism in a non-smoking healthy male Chinese population. Four polymorphisms CYP1 A2*1 C ( G-3860 A), G-3113 A, CYP1 A2*1 F ( C-163 A) and CYP1 A2*1 B ( C-5347 T) were screened in 238 unrelated male volunteers. Then, a single oral 200-mg dose of theophylline was administered to 37 volunteers, who were selected from 238 volunteers based on the CYP1 A2 genotype. CYP1 A2 activities were evaluated by plasma 1,7-dimethylxanthine/caffeine ratios (17 X/137 X) after administration of 100-mg caffeine. The plasma concentrations of theophylline, 17 X and 137 X were determined by high-performance liquid chromatography. The activity of CYP1 A2 was lower in volunteers with the -3113 AA genotype compared with those with the -3113 AG genotype (0.35 ± 0.04 versus 0.48 ± 0.07, p = 0.016) or the -3113 GG genotype (0.35 ± 0.04 versus 0.58 ± 0.22, p = 0.037). CYP1 A2*1 F polymorphisms were associated with increased CYP1 A2 activity in volunteers with -3860 G/-3113 G/5347 C homozygosity (0.66 ± 0.24 versus 0.46 ± 0.05, p = 0.034). However, theophylline metabolism showed no difference among volunteers carrying different haplotype pairs. CYP1 A2 genetic polymorphisms influenced CYP1 A2 enzyme activity as measured by caffeine, but CYP1 A2 gene polymorphisms appeared to have limited influence on theophylline metabolism in our study. [ABSTRACT FROM AUTHOR]